Novel 2-phenyl-imidazoles and pharmaceutical compositions containing same

• US 4,722,929 A
• Filed: 12/20/1984
• Issued: 02/02/1988
• Est. Priority Date: 12/28/1983
• Status: Expired due to Fees

• Current Assignee: Dr KARL Thomae GmbH D-7950 Biberach An Der RISS Germany A Corporation of
• Original Assignee: Dr. Karl Thomae GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: van Meel, Jacobus C. A., Hauel, Norbert, Heider, Joachim, Austel, Volkhard, Reiffen, Manfred, Diederen, Willi, Nickl, Josef
• Primary Examiner(s): Daus, Donald G.
• Assistant Examiner(s): Teoli, Jr., William A.
• Application Number:
  US06/684,052
• Time in Patent Office: 1,139 Days
• Field of Search: 546/118, 514/303
• US Class Current: 514/303
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 213/75 Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 239/545 with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 473/00 Heterocyclic compounds containing purine ring systems
• CPC Class Codes: C07D 473/04 two oxygen atoms
• CPC Class Codes: C07D 473/06 with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
• CPC Class Codes: C07D 473/40 with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

The invention relates to novel 2-phenyl-imidazoles of the formula ##STR1## and the tautomers and acid addition salts thereof, particularly the pharmacologically acceptable acid addition salts, which exhibit valuable pharmacological properties, particularly an effect on the contractility of the heart muscle. The compounds of Formula I may be prepared by methods conventionally used for similar compounds.

Claims

1. A compound of the formula ##STR15## wherein (a) A is nitrogen, B is hydroxymethine and D is methine;

or

(b) B is nitrogen, one of A and D is hydroxymethine and the other is methine;

R₁ is methylmercapto, methylsulfinyl, methylsulfonyl, aminosulfonyl, methylaminosulfonyl or dimethylaminosulfonyl;

R₂ is alkoxy of 1 to 3 carbon atoms; and

R₃ is hydrogen or methoxy;

a pyridone tautomer thereof;

or a non-toxic, pharmacologically acceptable acid addition salt thereof.

2. A compound of claim 1, which is of the formula ##STR16## wherein (a) A is nitrogen, B is hydroxymethine and D is methine;

or

(b) B is nitrogen, one of A and D is hydroxymethine and the other is methine;

R₁ is methylmercapto, methylsulfinyl, methylsulfonyl, aminosulfonyl, methylaminosulfonyl or dimethylaminosulfonyl; and

R₂ is alkoxy of 1 to 3 carbon atoms;

a pyridone tautomer thereof;

or a non-toxic, pharmacologically acceptable acid addition salt thereof.

3. A compound of claim 1, which is of the formula ##STR17## wherein R₁ is methylmercapto, methylsulfinyl, methylsulfonyl, aminosulfonyl, methylaminosulfonyl or dimethylaminosulfonyl;

R₂ is alkoxy of 1 to 3 carbon atoms; and

R₃ is hydrogen or methoxy;

a pyridone tautomer thereof;

or a non-toxic, pharmacologically acceptable acid addition salt thereof.

4. A compound of claim 3, which is of the formula ##STR18## wherein R₁ is methylmercapto, methylsulfinyl, methylsulfonyl, aminosulfonyl, methylaminosulfonyl or dimethylaminosulfonyl;

and

R₂ is alkoxy of 1 to 3 carbon atoms;

a pyridone tautomer thereof;

or a non-toxic, pharmacologically acceptable acid addition salt thereof.

5. A compound of claim 4, where

R₁ is aminosulfonyl, methylaminosulfonyl or dimethylaminosulfonyl;

and

R₂ is methoxy;

a pyridone tautomer thereof;

or a non-toxic, pharmacologically acceptable acid addition salt thereof.

6. A non-toxic, pharmacologically acceptable acid addition salt of a compound of claim 1 formed with an inorganic or organic acid.

7. A compound of claim 1, which is 2-(2-methoxy-4-methylsulfonyl-phenyl)-4H-imidazo[4,5-b]pyridine-5-one, a tautomer thereof or a non-toxic, pharmacologically acceptable acid addition salt thereof.

8. A compound of claim 1, which is 2-(2-methoxy-4-methylmercapto-phenyl)-4H-imidazo[4,5-b]pyridine-5-one, a tautomer thereof or a non-toxic, pharmacologically acceptable acid addition salt thereof.

9. A compound of claim 1, which is 2-(2-methoxy-4-dimethylaminosulfonyl-phenyl)-4H-imidazo[4,5-b]pyridine-5-one, a tautomer thereof or a non-toxic, pharmacologically acceptable acid addition salt thereof.

10. A cardiotonic pharmaceutical composition consisting essentially of an inert pharmaceutical carrier and an effective cardiotonic amount of a compound of claim 1.

11. The method of treating cardiac insufficiency in a warm-blooded animal in need of such treatment, which comprises perorally, parenterally or rectally administering to said animal an effective cardiotonic amount of a compound of claim 1.